This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is a worldwide epidemic of obesity, diabetes, and attendant serious complications, including cardiovascular disease. Type-1 diabetes mellitus (T1DM) is characterized by autoimmune-mediated [unreadable]-cell destruction, while T2DM is characterized by progressive [unreadable]-cell insufficiency. The transition from pre-diabetes to frank T2DM occurs when [unreadable]-cell function becomes inadequate to maintain insulin levels high enough to overcome peripheral insulin resistance. Thus, [unreadable]-cell failure is the critical defect in both T1 and T2DM. The successful treatment of T1DM and comprehensive therapy for T2DM will involve the propagation, maintenance, or restoration of [unreadable]-cell/islet function, which requires an understanding of the requirements for the survival, function, and potential expansion of intact islets ex vivo. We hypothesize that novel culture techniques will increase ex vivo primate islet survival and function and amenability to molecular analyses. We will address this hypothesis through the following specific aims. 1. Determine the effects of physiological O2 and microgravity/3-D culture on islet survival, integrity, and function. 2. Assess the effect of current diabetes therapies on the function of isolated primate islets. 3. Assess potential factors stimulating [unreadable]-cell replication. 4. Extrapolate non-human primate islet behavior to human islets. We have established successful protocols for islet isolation, assessment of islet viability, and glucose-stimulated insulin secretion. We are now initiating proposed studies on evaluation of various culture conditions on islet viability and function.